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Background Following years of sustained pressure on the UK health service, there is recognition amongst health professionals and stakeholders that current models of healthcare are likely to be inadequate going forward. Therefore, a fundamental review of existing social models of healthcare is needed to ascertain current thinking in this area, and whether there is a need to change perspective on current thinking. Method Through a systematic research review, this paper seeks to address how previous literature has conceptualized a social model of healthcare and, how implementation of the models has been evaluated. Analysis and data were extracted from 222 publications and explored the country of origin, methodological approach, and the health and social care contexts which they were set. Results The publications predominantly drawn from the USA, UK, Australia, Canada and Europe identified five themes namely: the lack of a clear and unified definition of a social model of health and wellbeing; the need to understand context; the need for cultural change; improved integration and collaboration towards a holistic and person-centred approach; measuring and evaluating the performance of a social model of health. Conclusion The review identified a need for a clear definition of a social model of health and wellbeing. Furthermore, consideration is needed on how a model integrates with current models and whether it will act as a descriptive framework or, will be developed into an operational model. The review highlights the importance of engagement with users and partner organizations in the co-creation of a model of healthcare. [ABSTRACT FROM AUTHOR]

Background During the first epidemic wave, COVID-19 surveillance focused on quantifying the magnitude and the escalation of a growing global health crisis. The scientific community first assessed risk through basic indicators, such as the number of cases or rates of new cases and deaths, and later began using other direct impact indicators to conduct more detailed analyses. We aimed at synthesizing the scientific community's contribution to assessing the direct impact of the COVID-19 pandemic on population health through indicators reported in research papers. Methods We conducted a rapid scoping review to identify and describe health indicators included in articles published between January 2020 and June 2021, using one strategy to search PubMed, EMBASE and WHO COVID-19 databases. Sixteen experts from European public health institutions screened papers and retrieved indicator characteristics. We also asked in an online survey how the health indicators were added to and used in policy documents in Europe. Results After reviewing 3891 records, we selected a final sample of 67 articles and 233 indicators. We identified 52 (22.3%) morbidity indicators from 33 articles, 105 severity indicators (45.1%, 27 articles) and 68 mortality indicators (29.2%, 51). Respondents from 22 countries completed 31 questionnaires, and the majority reported morbidity indicators (29, 93.5%), followed by mortality indicators (26, 83.9%). Conclusions The indicators collated here might be useful to assess the impact of future pandemics. Therefore, their measurement should be standardized to allow for comparisons between settings, countries and different populations. [ABSTRACT FROM AUTHOR]

Background Previous meta-analyses have indicated that aspirin could affect breast cancer outcomes, particularly when taken post-diagnostically. However, several recent studies appear to show little to no association between aspirin use and breast cancer mortality, all-cause mortality, or recurrence. Aims This study aims to conduct an updated systematic review and meta-analysis on the associations of pre-diagnostic and post-diagnostic aspirin use with the aforementioned breast cancer outcomes. It also looks, through subgroup analyses and meta-regressions, at a range of variables that could explain the associations between aspirin use and breast cancer outcomes. Results In total, 24 papers and 149 860 patients with breast cancer were included. Pre-diagnostic aspirin use was not associated with breast-cancer-specific mortality (HR 0.98, 95% CI, 0.80-1.20, P =.84) or recurrence (HR 0.94, 95% CI, 0.88-1.02, P =.13). Pre-diagnostic aspirin was associated with non-significantly higher all-cause mortality (HR 1.27, 95% CI, 0.95-1.72, P =.11). Post-diagnostic aspirin was not significantly associated with all-cause mortality (HR 0.87, 95% CI, 0.71-1.07, P =.18) or recurrence (HR 0.89, 95% CI, 0.67-1.16, P =.38). Post-diagnostic aspirin use was significantly associated with lower breast-cancer-specific mortality (HR 0.79, 95% CI, 0.64-0.98, P =.032). Conclusions The only significant association of aspirin with breast cancer outcomes is lower breast-cancer-specific mortality in patients who used aspirin post-diagnostically. However, factors such as selection bias and high inter-study heterogeneity mean that this result should not be treated as conclusive, and more substantial evidence such as that provided by RCTs is needed before any decisions on new clinical uses for aspirin should be made. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) promotion in healthcare systems is one of the priority areas highlighted by the World Health Organization, which recognizes that progress has been slow largely due to a lack of awareness and investment while requiring a system-based approach. Community pharmacies are one of the health structures that are more easily accessible to populations, thus constituting an ideal venue for developing health promotion activities. This research aimed to describe PA-enabling interventions developed in community pharmacies by pharmacists. Methods: An electronic search was performed in PubMed, Scopus, Web of Science, Cochrane and reference lists of the different papers until June 2023. Studies were eligible if performed in community pharmacies by pharmacists, focused on interventions aimed at increasing PA levels and if at least one PA-specific outcome was measured at two different time points. Results: We identified 7076 publications in the initial search, plus 31 records identified through backward citation tracking from relevant studies. After an initial screening, 236 were selected for full-text analysis. Of the 29 selected papers, 10 presented a low risk of bias for the measurement of PA levels. PA outcomes were generally self-reported outcomes where the change in terms of the percentage of individuals considered active or who increased PA because of the intervention. Conclusion: Several interventions to improve PA through community pharmacies were found although with a high level of heterogeneity and with only few with a low risk of bias. More targeted research that aims to capture PA levels and support the training of healthcare professionals is needed. [ABSTRACT FROM AUTHOR]

Background High-risk human papillomavirus (HR-HPV) is a known cause of cervical cancer (CC). Latvia has a high incidence of CC compared with the average incidence in the European Union. This study aims to fill the data gap on the HR-HPV burden in Latvia, providing information on its prevalence and associated factors. Methods The cross-sectional study was conducted from February 2021 to April 2022. Participants 25–70 years old visiting a general practitioner (general population) or those referred to a colposcopy clinic with changes in their cervical cytology (colposcopy population) collected vaginal self-sample and completed a paper-based questionnaire. Samples were analyzed with Cobas 6800 System (Roche) for HPV16, HPV18 and other HR-HPV (HPV31/33/35/39/45/51/52/56/58/59/66/68). Descriptive statistics for categorical variables were performed. The Chi-square test was used to determine for the statistical significance of differences in the proportions of the dependent variable between subgroups of the independent variable. Univariate and multivariate binary logistic regression were used to identify factors associated with positive HR-HPV status. Results were considered statistically significant at P  < 0.05. Results A total of 1274 participants provided a valid sample. The prevalence of any HR-HPV infection was 66.8% in the colposcopy group and 11.0% in the general population. Factors associated with positive HR-HPV status were marital status single/divorced/widowed (vs. married/cohabiting) [adjusted OR (aOR) 2.6; P  = 0.003], higher number of lifetime sex partners [aOR 5.1 (P  < 0.001) and 4.0 (P  = 0.001)] for six or more and three to five partners in the general population; in the colposcopy group, the statistical significance remained only for Latvian ethnicity (vs. other) (aOR 1.8; P  = 0.008) and current smoking (vs. never) (aOR 1.9; P  = 0.01). Conclusion We documented a comparison to European Union HR-HPV infection burden in Latvia. Any HR-HPV positivity was significantly associated with sexual and other health behavior. [ABSTRACT FROM AUTHOR]

Background The value equation of value-based healthcare (VBHC) as a single figure remains ambiguous, closer to a theoretical framework than a useful tool for decision making. The challenge lies in the way patient-centred outcomes (PCOs) might be combined to produce a single value of the numerator. This paper aims to estimate the weights of PCOs to provide a single figure in the numerator, which ultimately will allow a VBHC figure to be reached. Methods A cohort of patients diagnosed with breast cancer (n  = 690) with a 6-month follow-up recruited in 2019–20 across six European hospitals was used. Patient-reported outcomes (PROs), clinical-related outcomes (CROs), and clinical and socio-demographic variables were collected. The numerator was defined as a composite indicator of the PCOs (CI-PCO), and regression analysis was applied to estimate their weights and consequently arrive at a single figure. Results Pain showed as the highest weight followed by physical functioning , emotional functioning , and ability to work , and then by a symptom, either arm or breast. PCOs weights were robust to sensitivity analysis. The CI-PCO value was found to be more informative than the health-related quality of life (HRQoL) value. Conclusions To the best of our knowledge, this is the first research to combine the PCOs proposed by ICHOM to provide a single figure in the numerator of the value equation. This figure shows a step forward in VBHC to reach a holistic benchmarking across healthcare centres and a value-based payment. This research might also be applied in other medical conditions as a methodological pathway. [ABSTRACT FROM AUTHOR]

Background: With the increasing number of people affected by multiple chronic conditions, it is essential for public-health professionals to promote strategies addressing patient needs for coordinated care. We aim to explore preference heterogeneity for better-coordinated care delivery models in Swiss older adults, and identify profiles of individuals more open to healthcare reforms. Methods: A DCE (discrete choice experiment) survey was developed online and on paper for the Swiss adults aged 50þ, following best practice. To elicit preferences, we estimated a latent class model allowing grouping individuals with similar preferences into distinct classes, and examined what background characteristics contributed to specific class membership. Results: The optimal model identified three classes with different openness to reforms. Class 1 (49%) members were concerned with premium increases and were in favour of integrated care structures with care managed by interprofessional teams. Individuals in class 2 (19%) were younger, open to reforms, and expressed the needs for radical changes within the Swiss healthcare system. Class 3 respondents (32%) were strongly reluctant to changes. Conclusions: Our study goes beyond average preferences and identifies three distinct population profiles, a majority open to reforms on specific aspects of care delivery, a smallest group in favour radical changes, and a third strongly against changes. Therefore, tailored approaches around healthcare reforms are needed, e.g. explaining the role of interprofessional teams in coordinating care, electronic health records and insurance premium variation. [ABSTRACT FROM AUTHOR]

Background Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. Methods In the VOICE community—a European healthcare centre cluster intending to address VBHC from theory to practice—information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. Results Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. Conclusions To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions. [ABSTRACT FROM AUTHOR]

Background Despite the growing utilization of data-driven methods to investigate multimorbidity patterns, there is currently no consensus or guidance on the conditions to include when identifying patterns. This scoping review aims to systematically examine the nature of conditions included in existing studies using data-driven techniques. Methods A comprehensive search of three electronic databases (MEDLINE, Web of Science and Scopus) was conducted to identify relevant publications from inception to 28 February 2022 using predefined search terms and inclusion/exclusion criteria. The reference lists and citations of relevant papers were also searched. Results Among 7326 search results, 5444 relevant articles were identified. After screening against the eligibility criteria, 60 articles were included in the review. Half of the reviewed studies reported selection criteria for conditions, with prevalence in the population of interest being the most common criterion (40%). Most studies included at least one neurological [59 (98.3%)], musculoskeletal [58 (96.7%)], respiratory [57 (95.0%)] or mental health [56 (93.3%)] condition. In contrast, only a small proportion of studies included skin [17 (28.3%)], infections [14 (23.3%)] or autoimmune conditions [10 (16.7%)]. Nine conditions (hypertension, diabetes, cancer, arthritis, COPD, asthma, depression, stroke and osteoporosis) were included by more than half of the studies. Conclusions This review highlights the considerable heterogeneity among the conditions included in analyses of multimorbidity patterns. Researchers should provide a clear rationale for the selection of conditions to facilitate comparisons across studies and ensure reproducibility, as well as consider selecting a diverse range of conditions to capture the complexity of multimorbidity. [ABSTRACT FROM AUTHOR]

Background Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation. Materials and Methods In Study-309/KEYNOTE-775, patients received lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). The incidence and median time to the first onset of ARs, dose modifications, and concomitant medications are described. Key ARs characterized include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome. Results As expected, the most common any-grade key ARs included: hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Grades 3-4 key ARs with incidence ≥10% included: hypertension, fatigue, and weight decreased. Key ARs first occurred within approximately 3 months of treatment initiation. AR management strategies consistent with the prescribing information and the study protocol are discussed. Conclusion Successful AR management strategies for lenvatinib plus pembrolizumab include education of the patient and entire treatment team, preventative measures and close monitoring, and judicious use of dose modifications and concomitant medications. Clinicaltrials.gov ID NCT03517449 [ABSTRACT FROM AUTHOR]

For at least the past 5 decades, population genetics, as a field, has worked to describe the precise balance of forces that shape patterns of variation in genomes. The problem is challenging because modeling the interactions between evolutionary processes is difficult, and different processes can impact genetic variation in similar ways. In this paper, we describe how diversity and divergence between closely related species change with time, using correlations between landscapes of genetic variation as a tool to understand the interplay between evolutionary processes. We find strong correlations between landscapes of diversity and divergence in a well-sampled set of great ape genomes, and explore how various processes such as incomplete lineage sorting, mutation rate variation, GC-biased gene conversion and selection contribute to these correlations. Through highly realistic, chromosome-scale, forward-in-time simulations, we show that the landscapes of diversity and divergence in the great apes are too well correlated to be explained via strictly neutral processes alone. Our best fitting simulation includes both deleterious and beneficial mutations in functional portions of the genome, in which 9 % of fixations within those regions is driven by positive selection. This study provides a framework for modeling genetic variation in closely related species, an approach which can shed light on the complex balance of forces that have shaped genetic variation. [ABSTRACT FROM AUTHOR]

Aims Cardiovascular magnetic resonance parametric mapping enables non-invasive quantitative myocardial tissue characterization. Human myocardium has normal ranges of T1 and T2 values, deviation from which may indicate disease or change in physiology. Normal myocardial T1 and T2 values are affected by biological sex. Consequently, normal ranges created with insufficient numbers of each sex may result in sampling biases, misclassification of healthy values vs. disease, and even misdiagnoses. In this study, we investigated the impact of using male normal ranges for classifying female cases as normal or abnormal (and vice versa). Methods and results One hundred and forty-two healthy volunteers (male and female) were scanned on two Siemens 3T MR systems, providing averaged global myocardial T1 and T2 values on a per-subject basis. The Monte Carlo method was used to generate simulated normal ranges from these values to estimate the statistical accuracy of classifying healthy female or male cases correctly as 'normal' when using sex-specific vs. mixed-sex normal ranges. The normal male and female T1- and T2-mapping values were significantly different by sex, after adjusting for age and heart rate. Conclusion Using 15 healthy volunteers who are not sex specific to establish a normal range resulted in a typical misclassification of up to 36% of healthy females and 37% of healthy males as having abnormal T1 values and up to 16% of healthy females and 12% of healthy males as having abnormal T2 values. This paper highlights the potential adverse impact on diagnostic accuracy that can occur when local normal ranges contain insufficient numbers of both sexes. Sex-specific reference ranges should thus be routinely adopted in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction Standard investigator-based adverse events (AE) assessment is via CTCAE for clinical trials. However, including the patient perspective through PRO (patient-reported outcomes) enhances clinicians' understanding of patient toxicity and fosters early detection of AEs. We assessed longitudinal integration of PRO-CTCAE within clinical workflow in a phase II trial. Materials and methods As a sub-study in a phase II trial of genotype-directed irinotecan dosing evaluating efficacy in patients with metastatic colorectal cancer receiving FOLFIRI and bevacizumab, patients reported on 13 AEs generating a PRO-CTCAE form. The primary objective was to estimate forms completed by patients and clinicians at least 80% of time. Secondary objectives were estimating concordance and time to first score of specific symptoms between patient and clinician pairs. Results Feasibility of longitudinal PRO-CTCAE integration was met as 96% of patients and clinician-patient pairs completed at least 80% of PRO-CTCAE forms available to them with 79% achieving 100% completion. Concordance between patient and clinician reporting a severe symptom was 73% with 24 disconcordant pairs, 21 involved patients who reported a severe symptom that the clinician did not. Although protocol-mandated dose reductions were guided by CTCAE not PRO-CTCAE responses, the median time to dose reduction of 2.53 months, and the time-to-event curve closely approximated time to patient-reported toxicity. Conclusion Longitudinal integration of PRO-CTCAE paired CTCAE proved feasible. Compared to clinicians, patients reported severe symptoms more frequently and earlier. Patient-reported toxicity more closely aligned with dose decreases indicating incorporation into routine clinical practice may enhance early detection of toxicity improving patient safety and quality of life. [ABSTRACT FROM AUTHOR]

Tumor mutation profiling (MP) is often conducted on tissue from biopsies conducted for clinical purposes (diagnostic tissue). We aimed to explore the views of patients with cancer on who should own tumor biopsy tissue, pay for its storage, and decide on its future use; and determine their attitudes to and predictors of undergoing additional biopsies if required for research purposes. In this mixed methods, cross-sectional study, patients with advanced solid cancers enrolled in the Molecular Screening and Therapeutics Program (n  = 397) completed a questionnaire prior to undergoing MP (n  = 356/397). A subset (n  = 23) also completed a qualitative interview. Fifty percent of participants believed they and/or relatives should own and control access to diagnostic tissue. Most (65.5%) believed the government should pay for tissue preparation. Qualitative themes included (1) custodianship of diagnostic tissue, (2) changing value of tissue across time and between cultures, (3) equity regarding payment, and (4) cost-benefit considerations in deciding on additional biopsies. Policy and regulation should consider patient perspectives. Extension of publicly funded health care to include tissue retrieval for clinical trials should be considered. [ABSTRACT FROM AUTHOR]

Given the enormous scale of the COVID-19 pandemic affecting the healthcare sector, limited human resource capacity, and efforts to prevent the spread of COVID-19, occupational health protection could not escape changes. The aim was to identify and compare the regulations regarding the provision of medical occupational check-ups (MOCs) during the pandemic in all European Union member states (EU MS). The study employed the Delphi method, involving experts from EU MS to assess MOC regulations between January 2020 and May 2021. Experts were queried regarding the existence and specifics of MOC regulations, particularly for entrance and periodic MOCs at hazardous and non-hazardous workplaces. Out of the 27 EU MS surveyed, 13 EU MS did not regulate MOCs, while 14 EU MS (51.6%) regulated the provision of MOCs. The regulations were changes in the way MOCs were provided, modifications (postponement in time, alternative provision, e.g. using telemedicine or online connection, or replacing the medical certificate of fitness to work based on the MOC with a declaration by the worker), or interruption without compensation, even for hazardous works. The regulations were in effect for different lengths of time and varied in some countries during the study period. The cumulative duration of MOC interruptions in all EU MS during the study period was 137 months (7.5% of the cumulative study period of 1836 months). Given the different approaches to the provision of MOCs in EU MS, it has proved appropriate to develop an optimal unified framework plan for future similar situations. [ABSTRACT FROM AUTHOR]

Background Social inequalities in multimorbidity may occur due to familial and/or individual factors and may differ between men and women. Using population-based multi-generational data, this study aimed to (1) assess the roles of parental and individual education in the risk of multimorbidity and (2) examine the potential effect modification by sex. Methods Data were analysed from 62 060 adults aged 50+ who participated in the Survey of Health, Ageing and Retirement in Europe, comprising 14 European countries. Intergenerational educational trajectories (exposure) were High–High (reference), Low–High, High–Low and Low–Low, corresponding to parental–individual educational attainments. Multimorbidity (outcome) was ascertained between 2013 and 2020 as self-reported occurrence of ≥2 diagnosed chronic conditions. Inequalities were quantified as multimorbidity-free years lost (MFYL) between the ages of 50 and 90 and estimated via differences in the area under the standardized cumulative risk curves. Effect modification by sex was assessed via stratification. Results Low individual education was associated with higher multimorbidity risk regardless of parental education. Compared to the High–High trajectory, Low–High was associated with −0.2 MFYL (95% confidence intervals: −0.5 to 0.1), High–Low with 3.0 (2.4–3.5), and Low–Low with 2.6 (2.3–2.9) MFYL. This pattern was observed for both sexes, with a greater magnitude for women. This effect modification was not observed when only diseases diagnosed independently of healthcare-seeking behaviours were examined. Conclusions Individual education was the main contributor to intergenerational inequalities in multimorbidity risk among older European adults. These findings support the importance of achieving a high education to mitigate multimorbidity risk. [ABSTRACT FROM AUTHOR]

Background The Nordic countries represent a unique case study for the COVID-19 pandemic due to socioeconomic and cultural similarities, high-quality comparable administrative register data and notable differences in mitigation policies during the pandemic. We aimed to compare weekly excess mortality in the Nordic countries across the three full pandemic years 2020–2022. Methods Using data on weekly all-cause mortality from official administrative registers in Denmark, Finland, Norway and Sweden, we employed time series regression models to assess mortality developments within each pandemic year, with the period 2010–2019 used as reference period. We then compared excess mortality across the countries in 2020–2022, taking differences in population size and age- and sex-distribution into account. Results were age- and sex-standardized to the Danish population of 2020. Robustness was examined with a variety of sensitivity analyses. Results While Sweden experienced excess mortality in 2020 [75 excess deaths per 100 000 population (95% prediction interval 29–122)], Denmark, Finland and Norway experienced excess mortality in 2022 [52 (14–90), 130 (83–177) and 88 (48–128), respectively]. Weekly death data reveal how mortality started to increase in mid-2021 in Denmark, Finland and Norway, and continued above the expected level through 2022. Conclusion Although the Nordic countries experienced relatively low pandemic excess mortality, the impact and timing of excess mortality differed substantially. These estimates—arguably the most accurate available for any region in capturing pandemic-related excess deaths—may inform future research and policy regarding the complex mortality dynamics in times of a health crisis such as the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background During the 1997–2010 Labour government, several policies were implemented to narrow health inequalities as part of a national health inequalities strategy. Many of these policies are likely to have had a disproportionately large impact on people aged 65 and over. We aimed to understand the association between the health inequalities strategy period and inequalities in mortality at age 65–69. Methods We use population at risk and mortality data covering 1991–2019 to calculate mortality rate at age 65–69 at the Local Authority level. We use the 2019 Index of Multiple Deprivation to examine geographical inequalities. We employ segmented linear regression models with marginal spline terms for the strategy period and interact these with an indicator of deprivation to understand how inequalities changed before, during and after the strategy. The reporting of this study adheres to STROBE guidelines. Results Mortality rates in each deprivation quintile improved continuously throughout the period of study. Prior to the programme (1991–9) there was no significant change in absolute inequalities. However, during the strategy (2000–10) there was a significant decrease in absolute inequalities of −9.66 (−17.48 to −1.84). The period following the strategy (2011–19) was associated with a significant increase in absolute inequalities of 12.84 (6.60 to 19.08). Our results were robust to a range of sensitivity tests. Conclusion The English health inequalities strategy was associated with a significant reduction in absolute inequality in mortality age 65–69. Future strategies to address inequalities in ageing populations may benefit from adopting a similar approach. [ABSTRACT FROM AUTHOR]

Background For cancer screening programmes to be effective in early detection it is important that those invited can access screening services and understand the benefits of participation. A better understanding of the factors that matter to potential participants of cancer screening programmes can assist in developing strategies to increase current uptake. Methods We conducted an overview of systematic reviews to answer the question: What factors influence the uptake of cancer screening services (breast, bowel and cervical) in high-income countries? A thematic approach supported by tabular summaries and qualitative heat maps was used to categorize factors, described as 'barriers' or 'facilitators'. Results A total of 41 systematic reviews met the criteria for inclusion. The barrier with the greatest number of 'hot spots' across all three screening programmes was a fear of the unknown regarding a possible diagnosis of cancer or abnormal screening results, followed closely by a general lack of knowledge surrounding cancer screening programmes. The greatest collective facilitator to uptake was recommendation by a healthcare provider to attend screening. Conclusion Across all factors 'trust' and 'building trusted relationships' can be seen as integral to the success of cancer screening programmes and must be reflective of collaborative efforts to mitigate barriers and enhance facilitators to uptake. There is future scope to consider interventions that (i) increase demand for screening services, (ii) reduce barriers to uptake of services and/or (iii) are relevant to the healthcare system and those providing services. [ABSTRACT FROM AUTHOR]

Background Although the global chronic morbidity indicator (GCMI) of the Minimum European Health Module (MEHM) was not specifically designed to monitor chronic disease in the population, it is increasingly used for this purpose in Europe and elsewhere. However, its metrological characteristics have seldom been examined, with various sensitivity issues being raised. The present study investigated the metrological performances of the GCMI and analyzed its implications in terms of prevalence and demographic and socioeconomic gradients of chronic conditions in the population. Methods We used data from two large French nationwide representative surveys with cross-sectional and longitudinal data conducted between 2010 and 2021. The surveys used MEHM and collected data on numerous chronic conditions and socioeconomic indicators. Criterion and predictive validity of the GCMI regarding chronic conditions and the resultant socioeconomic gradients were compared with indicators based on reports of individual chronic conditions. Results GCMI sensitivity to capture chronic conditions varied from <20 to 80% depending on the chronic condition. Number of chronic conditions, gender, age and education were also associated with GCMI endorsement. However, the GCMI was predictive of mortality and activity limitations independently of individual conditions. Conclusion The varying lack of sensitivity depending on the chronic condition and the respondent's sociodemographic status may bias estimates of demographic and socioeconomic gradients compared with indicators based on reports of individual chronic conditions. Differences between GCMI and list-based approaches should be more cautiously considered when monitoring chronic conditions in the population. These approaches should be viewed as complementary rather than contradictory or interchangeable. [ABSTRACT FROM AUTHOR]

Background The American Heart Association recently released an updated algorithm for evaluating cardiovascular health—Life's Essential 8 (LE8). However, the associations between changes in LE8 score over time and risk of cardiovascular disease (CVD) remain unclear. Methods We investigated associations between 6-year changes (2006–12) in LE8 score and risk of subsequent CVD events (2012–20) among 53 363 Chinese men and women from the Kailuan Study, who were free from CVD in 2012. The LE8 score was calculated based on eight components: diet quality, physical activity, smoking status, sleep health, body mass index, blood lipids, blood glucose and blood pressure. Multivariable-adjusted Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results We documented 4281 incident CVD cases during a median of 7.7 years of follow-up. Compared with participants whose LE8 scores remained stable in a 6-year period, those with the large increases of LE8 score over the 6-year period had a lower risk of CVD, heart disease and stroke in the subsequent 8 years [HRs and 95% CIs: 0.67 (0.64, 0.70) for CVD, 0.65 (0.61, 0.69) for heart disease, 0.71 (0.67, 0.76) for stroke, all P trend < 0.001]. Conversely, those with the large decreases of LE8 score had 47%, 51% and 41% higher risk for CVD, heart disease and stroke, respectively. These associations were consistent across the subgroups stratified by risk factors. Conclusions Improving LE8 score in a short- and moderate-term was associated with a lower CVD risk, whereas decreased LE8 score over time was associated with a higher risk. [ABSTRACT FROM AUTHOR]

Background Aimed to compare the prevalence, characteristics, and associated mortality risk of frailty in Northern Ireland (NI) and the Republic of Ireland (ROI). Methods Secondary analysis of the first wave of two nationally representative cohorts, the Northern Ireland Cohort for the Longitudinal Study of Ageing or NICOLA study (N  = 8504) and the Irish Longitudinal Study on Ageing or TILDA study (N  = 8504). Frailty was assessed using a harmonized accumulation deficits frailty index (FI) containing 30 items. FI scores classified individuals as non-frail (<0.10), pre-frail (0.10–0.24) and frail (≥0.25). Linkage to respective administrative data sources provided mortality information with a follow-up time of 8 years. Results The prevalence of frailty was considerably higher in NI compared with the ROI (29.0% compared with 15.0%), though pre-frailty was slightly lower (35.8% and 37.3%, respectively). Age, female sex, and lower socio-economic status were consistently associated with a higher likelihood of both pre-frailty and frailty. In the pooled analysis, both frailty and pre-frailty were higher in NI (RR = 2.68, 95% CIs 2.45, 2.94 and RR = 1.30, 95% CIs 1.21, 1.40, respectively). Frailty was associated with an increased mortality risk in both cohorts, even after full adjustment for all other characteristics, being marginally higher in TILDA than in NICOLA (HR = 2.43, 95% CIs 2.03, 2.91 vs. HR = 2.31, 95% CIs 1.90, 2.79). Conclusions Frailty is a major public health concern for both jurisdictions. Further research and monitoring are required to elucidate why there is a higher prevalence in NI and to identify factors in early life that may be driving these differences. [ABSTRACT FROM AUTHOR]

Background Patients with intrahepatic cholangiocarcinoma (ICC) are prone to recurrence and poor survival. Targeted therapy related to isocitrate dehydrogenase (IDH) is an extremely important treatment. IDH1 and IDH2 mutations are generally thought to have similar effects on the tumor landscape. However, it is doubtful whether these 2 mutations have exactly the same effects on tumor cells and the tumor microenvironment. Methods All collected tumor samples were subjected to simultaneous whole-exon sequencing and proteome sequencing. Results IDH1 mutations accounted for 12.2%, and IDH2 mutations accounted for 5.5%, all missense mutations. Tumors with IDH mutations had lower proportions of KRAS and TP53 mutations. Mutated genes were obviously enriched in the kinase pathway in the tumors with IDH2 mutations. The signaling pathways were mainly enriched in the activation of cellular metabolic activities and an increase of inhibitory immune cells in the tumors with IDH mutations. Moreover, tumors had unique enrichment in DNA repair in IDH1 mutants and secretion of biological molecules in IDH2 mutants. Inhibitory immune cells might be more prominent in IDH2 mutants, and the expression of immune checkpoints PVR and HLA-DQB1 was more prominent in IDH1 mutants. IDH mutants were more related to metabolism-related and inflammation-immune response clusters, and some belonged to the DNA replication and repair cluster. Conclusions These results revealed the differential IDH1 and IDH2 mutation-related landscapes, and we have provided an important reference database to guide ICC treatment. [ABSTRACT FROM AUTHOR]

Background Blinded independent central review (BICR) of radiographic images is frequently conducted in oncology trials to address the potential bias of local evaluation (LE) of endpoints such as progression-free survival (PFS) and objective response rate (ORR). Given that BICR is a complex and costly process, we evaluated the agreement between LE- and BICR-based treatment effect results and the impact of BICR on regulatory decision-making. Materials and Methods Meta-analyses were performed using hazard ratios (HRs) for PFS and odds ratios (ORs) for ORR from all randomized Roche-supported oncology clinical trials during 2006-2020 that had both LE and BICR results (49 studies with a total of over 32 000 patients). Results Overall, the evaluation bias of LE overestimating the treatment effect compared with BICR based on PFS was numerically small and not clinically meaningful, especially for double-blind studies (HR ratio between BICR and LE: 1.044). A larger bias is more likely to occur in studies with open-label design, smaller sample sizes, or an unequal randomization ratio. The majority (87%) of the PFS comparisons led to the same statistical inference by BICR and LE. For ORR, a high degree of agreement between BICR and LE results was also observed (OR ratio of 1.065), although the agreement was slightly lower than for PFS. Conclusion BICR did not notably impact the study interpretation nor drive the sponsor's regulatory submission decisions. Hence, if bias can be diminished by appropriate means, LE is deemed as reliable as BICR for certain study settings. [ABSTRACT FROM AUTHOR]

Background Venous thromboembolism (VTE) is a leading cause of death in patients with cancer. Limited data exist about VTE in patients with adrenocortical carcinoma (ACC). The primary objective of this study was to identify the prevalence of VTE in a cohort of patients with ACC. Secondary objectives were to determine the impact of VTE events on overall survival (OS) and to describe the characteristics of VTE in patients with ACC. Patients and Methods We retrospectively reviewed data from 289 patients with ACC cared for at a major referral center from February 2010 to June 2022. Results VTE prevalence was 18.7% (54 events). Thirty patients (55.6%) had pulmonary embolism (PE); 12 patients (22.2%) had deep vein thrombosis (DVT); and 12 patients (22.2%) had both PE and DVT. VTE occurred after ACC diagnosis in 50 patients (92.6%) including 44 patients (88%) with stage 3 or 4 ACC. VTEs were CTCAE grade ≤2 in 32 cases (59.3%), grade 3 in 17 (31.5%), and grade 4 in 2 (3.7%). Thirteen patients (24%) died within 6 months after VTE diagnosis, although there was no statistically significant association between VTE and overall survival. Conclusion Despite the potential to underestimate the prevalence of VTEs, we found a high frequency of VTE events in patients with ACC. A majority of VTEs occurred in the context of advanced ACC and we observed high short-term mortality. Further studies are needed to validate our findings and investigate mechanisms associated with VTE in ACC. [ABSTRACT FROM AUTHOR]

Background As a newly identified subtype of HER2-negative tumors associated with a less favorable prognosis, it remains crucial to evaluate potential prognostic and predictive factors, particularly non-invasive biomarkers, for individuals with human epidermal growth factor 2 (HER2) low early-stage breast cancer (EBC). Multiple investigations have highlighted that HER2-negative patients with EBC exhibiting high homologous recombination deficiency (HRD) scores display lower rates of pathological complete response (PCR) to neoadjuvant chemotherapy (NAC). Nevertheless, no study to date has explored the correlation between HRD and the long-term prognosis in HER2-low patients with EBC. Patients and methods This retrospective observational study focuses on primary EBC sourced from The Cancer Genome Atlas dataset (TCGA). It reveals the gene mutation landscape in EBC with low HER2 expression and elucidates the tumor immune landscape across different HRD states. Utilizing bioinformatics analysis and Cox proportional models, along with the Kaplan-Meier method, the study assesses the correlation between HRD status and disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Subgroup analyses were conducted to identify potential variations in the association between HRD and prognosis. Results In the patients with HER2-low breast cancer, patients with homologous recombination related genes (HRRGs) defects had an HRD score about twice that of those without related genes mutations, and were at higher risk of acquiring ARID1A , ATM , and BRCA2 mutations. We also found that most immune cell abundances were significantly higher in EBC tumors with high HRD than in EBC tumors with low HRD or HRD-medium, particularly plasma B-cell abundance, CD8 T-cell abundance, and M1 macrophages. In addition, these tumors with HRD-high also appear to have significantly higher tumor immune scores and lower interstitial scores. Then, we analyzed the relationship between different HRD status and prognosis. There was statistical significance (P  = .036 and P  = .046, respectively) in DSS and PFI between the HRD-low and HRD-high groups, and patients with HRD-high EBC showed relatively poor survival outcomes. A medium HRD score (hazard ratio, HR = 2.15, 95% CI: 1.04-4.41, P  = .038) was a significant risk factor for PFI. Hormone receptor positivity is an important factor in obtaining medium-high HRD score and poor prognosis. Conclusion Higher HRD scores were associated with poorer PFI outcomes, particularly in people with HR+/HER2-low. Varied HRD states exhibited distinctions in HRRGs and the tumor immune landscape. These insights have the potential to assist clinicians in promptly identifying high-risk groups and tailoring personalized treatments for patients with HER2-low EBC, aiming to enhance long-term outcomes. [ABSTRACT FROM AUTHOR]

Objectives Cancer-related cognitive impairment (CRCI) refers to a cognitive decline associated with cancer or its treatments. While research into CRCI is expanding, evidence remains scattered due to differences in study designs, methodologies, and definitions. The present umbrella review aims to provide a comprehensive overview of the current evidence regarding the impact of different breast cancer therapies on cognitive functioning, with a particular focus on the interplay among objective cognitive deficits (ie, measured with standardized tests), subjective cognitive concerns, (ie, self-reported), and other mediating psycho-physical factors. Methods The search was made in Pubmed, Embase, and Scopus for articles published until July 2023, following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis protocol. Results Chemotherapy and endocrine therapy appear consistently associated with CRCI in patients with breast cancer, primarily affecting memory, attention/concentration, executive functioning, and processing speed. Subjective cognitive concerns were often found weakly or not associated with neuropsychological test results, while overall CRCI seemed consistently associated with psychological distress, fatigue, sleep quality, and inflammatory and biological factors. Conclusion Current evidence suggests that CRCI is common after chemotherapy and endocrine therapy for breast cancer. However, heterogeneity in study designs and the scarcity of studies on more recent treatments such as targeted therapies and immunotherapies, highlight the need for more systematic and harmonized studies, possibly taking into account the complex and multifactorial etiology of CRCI. This may provide valuable insights into CRCI's underlying mechanisms and potential new ways to treat it. [ABSTRACT FROM AUTHOR]

Background According to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, both immunohistochemical HER2 (3+) and HER2 (2+)/in situ hybridization (ISH) amplified [HER2 (2+)/ISH+] breast cancers (BCs) fall under the HER2-positive BC category. However, there is a lack of studies exploring the difference of neoadjuvant therapeutic response between patients with HER2 (3+) and HER2 (2+)/ISH+ early BC. We aimed to evaluate the neoadjuvant therapeutic response, long-term outcome, and intrinsic subtype heterogeneity between HER2 (3+) and HER2 (2+)/ISH+ BC. Methods We examined 2 distinct cohorts. Cohort 1 (C1) encompassed 2648 patients with HER2-positive early BC diagnoses, and they received neoadjuvant therapy (NT) and surgery between January 1, 2009 and December 31, 2022, from the Shanghai Jiao Tong University Breast Cancer Data Base. Cohort 2 (C2) comprised 135 patients with early-stage HER2-positive BC who underwent NT and surgery at Henan Cancer Hospital from January 1, 2021, to December 31, 2022. These patients had available genomic and transcriptomic data at their disposal. C1 and C2 were further categorized into 2 patient cohorts as follows: (1) patients with IHC HER2 (3+) early BC [HER2 (3+) group], (2) patients with HER2 (2+)/ISH+ early BC [HER2 (2+)/ISH+ group]. Among those excluded from the analysis were patients < 18 years or >80 years of age. Clinicopathological parameters, long-term outcomes, and intrinsic subtypes were analyzed. Results In the C1 population, 83.7% had HER2 (3+) BC, while 16.3% had HER2 (2+)/ISH+ BC. Patients with HER2 (3+) had a significantly higher pathological complete response (PCR) rate (38.9%) than patients with HER2 (2+)/ISH+ (18.1%; P  < .001), but the disease-free survival (DFS) was comparable after a median follow-up of 29 months (P  = .556). The addition of trastuzumab or trastuzumab plus pertuzumab to neoadjuvant chemotherapy (NAC) improved PCR rates and DFS in HER2 (3+) BC but not in HER2 (2+)/ISH+ BC. In the C2 population, 97.75% HER2 (3+) and 52.17% HER2 (2+)/ISH+ were HER2 enriched (HER2E) subtype (P  < .001). HER2E showed increased PCR rates compared to non-HER2E (P  = .004). Conclusions Compared to HER2 (3+) BC, the limited effectiveness of neoadjuvant trastuzumab and pertuzumab therapy for HER2 (2+)/ISH+ BC is due to subtype heterogeneity. Reassessment of targeted therapy efficacy in patients with HER2 (2+)/ISH+ BC is essential. [ABSTRACT FROM AUTHOR]

Background Although the long-term consequences of the Coronavirus Disease-2019 (COVID-19) pandemic are yet to be fully comprehended, a syndrome symptomatically akin to the COVID-19 disease has been defined, for children and adolescents, in February 2023 by the World Health Organization (WHO) as 'post COVID-19 condition' (PCC). Potential consequences of COVID-19 that affect developmental milestones in children and adolescents should be comprehended in their magnitude and duration. The aim is to investigate the most common symptoms and predictors or risk factors for pediatric PCC. Methods In this umbrella review, the population of interest was defined as children and adolescents from 0 to 19 years old presenting PCC symptoms as defined by the WHO in the International Classification of Diseases. The intervention considered was general follow-up activity to monitor the patients' recovery status. No comparator was chosen, and the outcomes were symptoms of PCC and predictors or risk factors of developing PCC. Methodological quality, risk of bias and the level of overlap between studies were assessed. A random-effects meta-analytic synthesis of respective estimates with inverse variance study weighting was carried out, for the primary studies included by the reviews retrieved, regarding predictors or risk factors reported. Results We identified six eligible systematic reviews, five with meta-analyses, from three databases. The most common symptoms reported were fatigue and respiratory difficulties; female sex and older age were the most reported factors associated with the development of pediatric PCC. Conclusions A deeper understanding of pediatric PCC requires well-designed and clearly defined prospective studies, symptom differentiation, and adequate follow-up. [ABSTRACT FROM AUTHOR]

Background This study aimed to describe the mortality excess during the three first epidemic periods of COVID-19 in all regions of France. Methods Two complementary approaches were implemented. First, we described the number of death of patients infected with or diagnosed with COVID-19 in health care (HC) and medico-social (MS) institutions. Then, we estimated general all-cause mortality excess (all ages) by comparing the mortality observed with the expected mortality. We used a daily number of death model according to a negative binomial distribution, as a function of the long-term trend in mortality (penalized spline function of time) and its seasonal variation (cyclic spline function). The model provided expected mortality during epidemic periods with a 95% credibility interval. Each region defined three epidemic periods, including the overseas territories. Results The two approaches were consistent in the most affected regions but there are major regional disparities that vary according to the epidemic period. There is an east–west gradient in the relative excess of deaths from all-causes during each epidemic period. The deaths observed in HC and MS institutions alone do not explain the excess (or deficit) of mortality in each region and epidemic period. Conclusion An analysis by age group according to the two approaches and a comparison of death specific causes could provide a better understanding of these differences. Electronic death registration system (mortality by medical causes) would allow a rapid mortality related estimation to an emerging pathology like Coronavirus Disease-2019 (COVID-19) but is still insufficient for real-time medical causes of death monitoring. [ABSTRACT FROM AUTHOR]

Background Complementary feeding has long-term effects on health but there is heterogeneity in recommendations across Europe. Recommendations include responsive feeding practices and nutritional needs but there is a debate in primary paediatricians as to which one should be the main criterion for complementary feeding. This pilot study investigated (i) the factors affecting the recommendations of paediatricians in Cyprus for starting complementary feeding, (ii) whether their main criterion is the developmental readiness or the nutritional needs of the infant and (iii) how this priority influences recommendations. Methods The 11-item questionnaire was completed by 73 Cypriot paediatricians. Results Approximately 66% of paediatricians recommended starting complementary feeding between 5 and 6 months, 29% between 4 and 5 and 3% between 6 and 7 months. Predefined schemes were recommended by ∼25% of paediatricians, baby-led weaning by 14% and 58% of paediatricians recommended either modality depending on the family circumstances whilst 4% involve the mother in the decision process. Approximately 64% of paediatricians recommended the introduction of parent's diet after the first year of life. Approximately 55% of paediatricians chose developmental readiness and 45% nutritional needs of the infant as their primary criterion for starting complementary feeding. Paediatricians who prioritized developmental readiness were more likely to be younger, less likely to advice on meat quantity and less likely to follow good nutritional practice. Conclusions The younger the paediatrician the more likely they are to prioritize developmental readiness over nutritional needs of the infant for complementary feeding. Paediatricians who prioritized developmental readiness were also less likely to provide nutritional advice. [ABSTRACT FROM AUTHOR]

Background Socioeconomic inequalities constitute an important focus area for public health, and it has long been established that higher educational level and longer lifespan are correlated. Little is known about decennial time trends in poor self-rated health and mental distress. Methods This study linked decennial cross-sectional survey data on self-rated health and mental distress from the Trøndelag Health Study (HUNT) from 1984 to 2019 with educational registry data using personal identification numbers. Survey participation ranged from 50 807 to 77 212. Slope index of inequality (SII) and relative index of inequality (RII) were calculated using generalized linear models in Stata. Analyses were stratified by sex and age, using the age categories of 30–59 years and 60–80 years. Results Absolute inequalities in self-rated health and mental distress between educational groups have stayed relatively stable throughout all rounds of HUNT. Relative inequalities in self-rated health and mental distress have generally increased, and both men and women with the lowest education level were more likely to experience poor self-rated health and mental distress relative to those with the highest education level. RII in self-rated health increased over time for both sexes and both age groups. RII for mental distress increased in both sexes and both age groups, except for men and women aged 60–80. Discussion This study shows that relative inequalities in self-rated and mental health in the Norwegian population are still persistent and have increased. Further knowledge about groups with a disadvantageous health situation should have implications for health care resource allocation. [ABSTRACT FROM AUTHOR]

Background During the Coronavirus Disease 2019 (COVID-19) pandemic, immunization programmes struggled to reach all population groups equally. While migrant groups face multiple barriers to health systems, including vaccination, little is known about their vaccine uptake. Methods We conducted a cross-sectional telephone survey on adults with and without migration history in Germany to investigate barriers and drivers to COVID-19 vaccination (11 April 2021 to 18 December 2021). Interviews were conducted in six languages. We used logistic regression models and a mediation model to analyze the association between migration history and vaccine uptake. Furthermore, we determined the effect of psychological determinants (5C model) on vaccine uptake. Results The survey comprised 2039 individuals, including 1015 with migration history. Of these, 448 were interviews conducted in languages other than German. Individuals with migration history had a significantly lower vaccine uptake but, while still unvaccinated, had a higher intention to get vaccinated (P  = 0.015) compared with those without migration history. The association between migration history and vaccine uptake was no longer significant when other factors were included in the regression model (odds ratio = 0.9; 95% confidence interval: 0.57–1.47). Socio-economic index, language skills and discrimination experience fully mediated this association. Among the psychological determinants, 'higher confidence' and 'higher collective responsibility' increased the chance of individuals with migration history to be vaccinated. Conclusion Migration history alone cannot explain vaccine uptake; socio-economic index, language skills and discrimination experiences need to be considered. To achieve vaccine equity, future public health policy should aim to reduce relevant barriers through tailored interventions. [ABSTRACT FROM AUTHOR]

Background Ribociclib is approved for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer (ABC) treatment, in combination with endocrine therapy. Hematological, hepatic, and cardiac adverse events (AEs) emerged from pivotal trials, but little is known about cutaneous adverse events (CAEs). Patients and Methods We report data from a retrospective cohort study of all patients with HR+/HER2− ABC treated with ribociclib at Humanitas Cancer Center between June 2017 and December 2022. We recorded clinical-pathological data, the incidence, and treatment of ribociclib-related CAEs. These were evaluated according to the NCI-CTCAE v5.0 classification. Progression-free survival (PFS) was estimated by Kaplan-Meier method and the log-rank test was used to analyze differences between groups. Results Thirteen of 91 patients (14.3%) experienced treatment-related CAEs (mean time to the occurrence: 3.9 months). The most frequent CAEs were eczematous dermatitis (53.8%) and maculo-papular reaction (15.4%). Itch was reported by all 13 patients. The grade was G3 in 8 cases, G2 in 4, and G1 in 1. An integrated approach based on ribociclib dose modulation and dermatological interventions (oral antihistamine, moisturized cream, topical, and/or systemic steroids) could prevent ribociclib discontinuation in most patients. At a median follow-up of 20 months, the median PFS was 13 months (range, 1-66) with a better PFS curves for patients experiencing CAEs (P  = .04). Conclusion We mapped frequency and types of ribociclib-induced CAEs. An interdisciplinary management of CAEs incorporated into routine care may reduce the rate of drug discontinuation thus potentially contributing to better long-term outcomes. [ABSTRACT FROM AUTHOR]

Background Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems. Methods Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of covariates that impacted OS and a validation set. Cox models were used to determine the association of various factors with OS and a scoring system was created. Results We identified 383 patients with HCC with imaging and survival outcomes, n  = 255 in the training set and 128 in the validation cohort. Factors associated with OS on multivariate analysis included: tumor margin appearance on CT or MRI (hazard ratio [HR] 1.37, 95% CI, 1.01-1.88) with infiltrative margins portending worse outcomes than encapsulated margins, massive tumor morphology (HR 1.64, 95% CI, 1.06-2.54); >2 lesions (HR 2.06, 95% CI, 1.46-2.88), Child-Turcotte-Pugh class C (HR 3.7, 95% CI, 2.23-6.16), and portal vein thrombus (HR 2.41, 95% CI, 1.71-3.39). A new scoring system was developed and more predictive of OS than other well-established systems. Conclusions Incorporation of standardized imaging characteristics to established clinical and lab predictors of outcome resulted in an improved predictive scoring system for patients with HCC. [ABSTRACT FROM AUTHOR]

Background Our previous work indicated that the addition of lobaplatin to combined therapy with taxane and anthracycline can improve the pathological complete response rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are unclear. Methods Eighty-three patients who met the inclusion criteria were included in this post hoc analysis. We analyzed the association between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) before neoadjuvant chemotherapy with the efficacy and prognosis after treatment with docetaxel, epirubicin, and lobaplatin neoadjuvant chemotherapy regimen. χ2 test and Cox regression were used to analyze the association between PLR and NLR with total pathologic complete response (tpCR), as well as the association between PLR and NLR with event-free survival (EFS) and overall survival (OS), respectively. Results The tpCR rate in the PLR− group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% [8/32], P  = .032). The tpCR rate in the NLR− group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% [7/30], P  = .024). The tpCR rate of the PLR−NLR− (PLR− and NLR−) group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ (PLR+ or/and NLR+) group (26.1% [11/42]; P  = .012). EFS and OS in the NLR+ group were significantly shorter than those in the NLR− group (P  = .028 for EFS; P  = .047 for OS). Patients in the PLR−NLR− group had a longer EFS than those in the PLR+/NLR+ group (P  = .002). Conclusion PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with the taxane, anthracycline, and lobaplatin regimen for patients with TNBC, as patients who had lower PLR and NLR values had a higher tpCR rate and a better long-term prognosis. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) caused major disruptions in healthcare services worldwide. Yet, little is known about the association between perceived disruption in healthcare services and sociodemographic factors, pre-existing health conditions as well as concurrent physical and psychological symptoms. Methods: Leveraging data from the Icelandic COVID-19 National Resilience Cohort, we performed a repeated measure analysis among 15 754 participants who responded to the question on perceived disruption in healthcare services from December 2020 to July 2021, to explore its association with socio-demographic factors, health indicators and conditions. Furthermore, we performed a longitudinal analysis among 7848 participants with two repeated measures to explore the association between timing and duration of perceived disruption in healthcare services and changes in depression, anxiety, sleep quality and somatic symptoms. Results: The prevalence of perceived disruption in healthcare services slightly decreased over time (P<0.01). Perceived disruption in healthcare services was more prevalent among individuals with pre-existing health conditions, i.e. history of psychiatric disorders (prevalence ratio=1.59, 95% confidence interval 1.48-1.72) and chronic somatic conditions [1.40 (1.30-1.52)]. However, no increase in the prevalence of perceived disruption in healthcare services was observed among individuals diagnosed with COVID-19 [0.99 (0.84-1.18)]. Moreover, we found that emerging perceived disruption in healthcare services was associated with an increase in symptoms of mental illness during the pandemic (bs 0.06-0.68). Conclusions: A disruption in healthcare services during the COVID-19 pandemic was reported by vulnerable groups, while the Icelandic healthcare system managed to maintain accessible services to individuals with COVID-19. [ABSTRACT FROM AUTHOR]

Background: Transport injuries are a major cause of mortality among adolescents. Our aim was to evaluate the circumstances and trauma associated with fatal accidents involving adolescents and two-wheeled vehicles. Methods: We analyzed retrospective data from the Finnish Crash Data Institute from 2008 to 2019 involving 10- to 24-year-old victims of fatal traffic accidents who were injured while riding a bicycle, moped or motorcycle. We collected data on patient characteristics, accident circumstances and possible treatment. These fatalities were compared with national mortality rates among the respective age groups. Results: We identified 147 fatalities over the 12-year period involving 20 bicycle, 50 moped and 77 motorcycle riders. Most accidents involved males (n=121, 82%). Less than half of vehicles were in good condition (46%); motorized vehicles were often illegally tuned (37%) or had tire problems (31%). Most of the accidents were collisions with another vehicle (n=99, 67%) or other objects (n=35, 24%). In 94% of cases, the Injury Severity Score was >25. Head injury was the most common cause of death (62%). Among 15-year-olds, every fifth death was due to accidents on two-wheeled vehicles. Conclusions: Fatal transport accidents among adolescents comprise several elements that should be incorporated into driver's education and in case of minors, also communicated to parents. These include the condition of the vehicle, proper helmet use and effects of speed on both control of the vehicle and the consequences of a possible collision. [ABSTRACT FROM AUTHOR]

Purpose The clinical efficacy of anti-CD20 radioimmunotherapy (RIT) is due to a combination of extracellular mechanisms involving immune-mediated cytotoxicity, and intracellular mechanisms related to inhibition of CD20 signaling and DNA damage from ionizing radiation. In 2002, the first RIT was approved by the U.S. Food and Drug Administration for the treatment of patients with indolent B-cell follicular non-Hodgkin lymphoma (NHL). The 2 approved agents, 90 Y-ibritumomab tiuxetan (90Y-IT, Zevalin, Acrotech Biopharma) and 131 I-tositumomab (131-IT, Bexxar, GlaxoSmithKline) both target CD20. The aim of this study was to review the clinical applications and supporting clinical trial data of anti-CD20 RIT for lymphoma. Methods A review of published articles and abstracts on the clinical efficacy and safety of 90Y-IT and iodine I 131 tositumomab was performed. Results The clinical efficacy and safety of anti-CD20 RIT have been demonstrated in numerous clinical trials and case series. Agents have produced significant responses in patients with follicular NHLs and in off-label applications. Importantly, RIT has demonstrated promising findings in high-risk lymphomas and heavily pretreated and refractory patient populations. Associated toxicity profiles are noted as tolerable, acceptable, and most often reversible. Conclusions In the 2 decades since its approval, anti-CD20 RIT continues to demonstrate efficacy, particularly with a proportion of patients maintaining long-term remissions. The combination of prolonged efficacy, tolerability, and treatment convenience makes RIT a reasonable alternative to other systemic therapies. It is recommended that further research on RIT should focus on biomarkers of long-term response, pretargeting, and sequencing of RIT in the treatment course. [ABSTRACT FROM AUTHOR]

Background Adolescent and young adult cancer survivors (AYAs, aged 18-39 years at first diagnosis) have a higher second cancer risk. Accelerated aging is hypothesized as underlying mechanism and has been described clinically by 6 indicators; fatigue, low quality of sleep, low mood, lack of motivation, subjective memory complaints, and poor exercise tolerance. Using patient-reported outcomes, we aimed to identify clusters of accelerated aging among AYA cancer survivors and to investigate their association with second cancer development. Patients and Methods Patient, tumor, and treatment data were obtained from the Netherlands Cancer Registry. Patient-reported clinical indicators and second cancer data were obtained from the SURVivors (5-20 years) of cancer in AYAs (SURVAYA) questionnaire study between 1999 and 2015. Latent class and multivariable logistic regression analyses were performed. Results In total, n  = 3734 AYA survivors with known second cancer status (n  = 278 [7.4%] second cancers) were included. Four latent clusters were identified and named based on their clinical indicator features; (1) high accelerated aging (31.3%), (2) intermediate accelerated aging without poor exercise tolerance (15.1%), (3) intermediate accelerated aging without lack of motivation (27.4%), and (4) low accelerated aging (26.2%). AYAs in the high accelerated aging cluster were more likely to have second cancer (odds ratio: 1.6; 95% CI, 1.1-2.3) compared to the low accelerated aging cluster. Conclusion AYAs with a higher burden of accelerated aging were more likely to develop a second cancer. Validation of the clinical indicators and how to best capture them is needed to improve (early) detection of AYAs at high risk of developing second cancer. [ABSTRACT FROM AUTHOR]

Introduction The aim of this systematic review was to summarize the current literature on wearable technologies in oncology patients for the purpose of prognostication, treatment monitoring, and rehabilitation planning. Methods A search was conducted in Medline ALL, Cochrane Central Register of Controlled Trials, Embase, Emcare, CINAHL, Scopus, and Web of Science, up until February 2022. Articles were included if they reported on consumer grade and/or non-commercial wearable devices in the setting of either prognostication, treatment monitoring or rehabilitation. Results We found 199 studies reporting on 18 513 patients suitable for inclusion. One hundred and eleven studies used wearable device data primarily for the purposes of rehabilitation, 68 for treatment monitoring, and 20 for prognostication. The most commonly-reported brands of wearable devices were ActiGraph (71 studies; 36%), Fitbit (37 studies; 19%), Garmin (13 studies; 7%), and ActivPAL (11 studies; 6%). Daily minutes of physical activity were measured in 121 studies (61%), and daily step counts were measured in 93 studies (47%). Adherence was reported in 86 studies, and ranged from 40% to 100%; of these, 63 (74%) reported adherence in excess of 80%. Conclusion Wearable devices may provide valuable data for the purposes of treatment monitoring, prognostication, and rehabilitation. Future studies should investigate live-time monitoring of collected data, which may facilitate directed interventions. [ABSTRACT FROM AUTHOR]

Introduction Cancer is a major public health problem in Rwanda and other low- and middle-income countries (LMICs). While there have been some improvements in access to cancer treatment, the cost of care has increased, leading to financial toxicity and treatment barriers for many patients. This study explores the financial toxicity of cancer care in Rwanda. Methods This prospective cross-sectional study was conducted at 3 referral hospitals in Rwanda, which deliver most of the country's cancer care. Data were collected over 6 months from June 1 to December 1, 2022 by trained research assistants (RAs) using a modified validated data collection tool. RAs interviewed consecutive eligible patients with breast cancer, cervical cancer, colorectal cancer, Hodgkin's and non-Hodgkin's lymphoma who were on active systemic therapy. The study aimed to identify sources of financial burden. Data were analyzed using descriptive statistics. Results 239 patients were included; 75% (n  = 180/239) were female and mean age was 51 years. Breast, cervix, and colorectal cancers were the most common diagnoses (42%, 100/239; 24%, 58/239; and 24%, 57/239, respectively) and 54% (n  = 129/239) were diagnosed with advanced stage (stages III-IV). Financial burden was high; 44% (n  = 106/239) of respondents sold property, 29% (n  =  70/239) asked for charity from public, family, or friends, and 16% (n  = 37/239) took loans with interest to fund cancer treatment. Conclusion Despite health insurance which covers many elements of cancer care, a substantial proportion of patients on anti-cancer treatment in Rwanda experience major financial toxicity. Novel health financing solutions are needed to ensure accessible and affordable cancer care. [ABSTRACT FROM AUTHOR]

Introduction The primary objective of this study was to determine whether workplace culture in academic oncology differed by gender, during the COVID-19 pandemic. Materials and Methods We used the Culture Conducive to Women's Academic Success (CCWAS), a validated survey tool, to investigate the academic climate at an NCI-designated Cancer Center. We adapted the CCWAS to be applicable to people of all genders. The full membership of the Cancer Center was surveyed (total faculty = 429). The questions in each of 4 CCWAS domains (equal access to opportunities, work-life balance, freedom from gender bias, and leadership support) were scored using a 5-point Likert scale. Median score and interquartile ranges for each domain were calculated. Results A total of 168 respondents (men = 58, women = 106, n = 4 not disclosed) submitted survey responses. The response rate was 39% overall and 70% among women faculty. We found significant differences in perceptions of workplace culture by gender, both in responses to individual questions and in the overall score in the following domains: equal access to opportunities, work-life balance, and leader support, and in the total score for the CCWAS. Conclusions Our survey is the first of its kind completed during the COVID-19 pandemic at an NCI-designated Cancer Center, in which myriad factors contributed to burnout and workplace challenges. These results point to specific issues that detract from the success of women pursuing careers in academic oncology. Identifying these issues can be used to design and implement solutions to improve workforce culture, mitigate gender bias, and retain faculty. [ABSTRACT FROM AUTHOR]

Background A measles epidemic affected the Nouvelle-Aquitaine region from November 2017 to May 2018 with clusters among Travellers. This indicates that measles vaccination rates among Travellers remain lower than in the general population. The objective of this study was to estimate the 'declarative vaccination' against measles, mumps and rubella (MMR) and to propose a conceptual framework to help identify determinants of MMR vaccination uptake among adult Travellers in Nouvelle-Aquitaine in 2019–20. Methods A cross-sectional study using random sampling was performed and included 612 adult Travellers from 1 November 2019 to 31 March 2020. A conceptual framework to model vaccination adherence was tested among this underserved population by using structural equation modelling. This model included five latent variables: health literacy, attitudes toward preventive measures, stigma, accessibility to care and perceived needs and five measured variables: information received on vaccination, perception of barriers, support for administrative documents, social support and housing conditions. Results Individuals who did not answer all the questions linked to the variables included in the model were excluded, thus 347 adults were included in the final sample. The declared vaccination rate against MMR was 74.0%, and 72.4% of the participants were favorable to vaccination. Vaccination adherence was significantly correlated with favorable attitudes toward preventive measures such as having a history of MMR vaccination and not having already refused a recommended vaccine and finally satisfactory information received on vaccination. Discussion To improve vaccination adherence, health authorities should lean on personal history with vaccination and on transmitting information on vaccination. [ABSTRACT FROM AUTHOR]

Background With the rapid development of the global economy and the acceleration of urbanization, air pollution has become a major environmental problem threatening human health. There is limited evidence on the acute effects of air pollution on chronic obstructive pulmonary disease (COPD). Methods From 2014 to 2019, we collected data on daily admissions for COPD patients from a city in China. We used the generalized additive model together with distributed lag models to fit the associations of air pollutants with hospital admissions. Results We observed significant increments in the number of daily admissions (0.086–0.109%) for COPD for a unit range increase in air quality index, PM 2.5 and PM 10 over four lag days. The impact of air pollution on the number of daily admissions was mainly reflected in the COPD patients who were hospitalized through outpatient departments and tertiary hospitals. Discussion Short-term exposure to outdoor air pollution may induce the occurrence or exacerbation of COPD patients; therefore, government departments should strengthen the management of air pollution, improve supervision and control mechanisms, pay attention to the quality of medical services, and reduce the adverse effects of air pollution on patients' health. [ABSTRACT FROM AUTHOR]

Background A growing number of studies have underlined the relationship between socioeconomic status and health. Following that literature, we explore the causal effect of financial hardships on changes in health at older ages. Rather than traditional measures of socioeconomic variables, we study the role of financial hardships. The declarative measurement of financial hardships is particularly relevant for assessing the impact of short-term financial difficulties on health among older adults. Methods In this study, we use data from the Lausanne cohort 65+. Participants are community-dwelling older adults representative of the population aged 65–70 years in 2004 and living in Lausanne (Switzerland) (n  = 1352). We use longitudinal annual data with 11 years of follow-up (2006–16) to estimate dynamic panel models on several indicators measuring older adults' health (self-rated health, number of medical conditions, depressive symptoms, difficulties with daily living activities). Results We find evidence of causal effects of financial hardships on self-rated health (coef. = 0.059, P  < 0.10) and on depressive symptoms (coef.=0.060, P  < 0.05). On the other hand, we find no evidence of causality running from financial hardships to the number of medical conditions and the difficulties in daily living activities. Conclusion These results make a contribution to the literature where nearly all previous research on associations between financial hardship and health does not establish causal relationships. Our results support the need to integrate health policies that mitigate the potential adverse health effects of financial hardship for older adults. [ABSTRACT FROM AUTHOR]

Background Adolescent mental health (AMH) needs in England have increased dramatically and needs exceed treatment availability. This study undertook a comparative assessment of the health and economic return on investment (ROI) of interventions to prevent and treat mental disorders among adolescents (10–19 years) and examined intervention affordability and readiness. Methods Interventions were identified following a review of published and grey literature. A Markov model followed a simulated adolescent cohort to estimate implementation costs and health, education, and economic benefits. Intervention affordability was assessed, comparing annual cost per adolescent with NHS England per capita spending, and an expert panel assessed intervention readiness using a validated framework. Results Over 10- and 80-year horizons, interventions to treat mild anxiety and mild depression were most cost-effective, with the highest individual lifetime ROI (GBP 5822 GBP 1 and GBP 257: GBP 1). Preventing anxiety and depression was most affordable and 'implementation ready' and offered the highest health and economic benefits. A priority package (anxiety and depression prevention; mild anxiety and mild depression treatment) would avert 5 million disability-adjusted life-years (DALYS) and achieve an ROI of GBP 15: GBP 1 over 10 years or 11.5 million DALYs (ROI of GBP 55: GBP 1) over 80 years. Conclusion The economic benefits from preventing and treating common adolescent mental disorders equivalent to 25% of NHS England's annual spending in 2021 over 10 years and 91% over 80 years. Preventing and early treatment for anxiety and depression had the highest ROIs and strong implementation readiness. [ABSTRACT FROM AUTHOR]

Advancements in genomics have significant implications for public health, making citizens' education vital for informed decision-making. Based on two literature reviews' findings and a survey conducted with experts from the Italian Network of Genomics in Public Health, we conducted a pilot survey on Italian citizens' attitudes, knowledge and educational needs toward genetic testing and omics sciences. Our results demonstrate a widespread interest in genetic testing and uncertainties regarding associated risks, with 99% of participants acknowledging insufficient knowledge of genetic testing. There is an urgent need for educational tools to improve citizens' literacy and engagement in this rapidly evolving field. [ABSTRACT FROM AUTHOR]

Background The public health workforce (PHW) needs to have the necessary capacities to provide healthcare services and public health services. Training needs assessments (TNA) is necessary to assess and understand PHW and their capacities to provide services. This review attempts to identify and describe published studies on tools and methodologies for TNA of the workforce used in public health and health-related fields. Methods A systematized review of literature was carried out in February 2022. Cochrane Handbook for systematic review version 5.2.0 and PRISMA 2020 statement were used to guide reporting. This review includes original research, reports and grey literature from the websites of public health organizations in English. Results This review included 38 documents for evidence synthesis. Twenty-seven documents were indexed literature (71%) and 11 were grey documents (29%). TNA documents were published between 1999 and 2022. TNA was performed in many countries around the world. The organizations used either a validated questionnaire or created their own tools to perform organizational and individual self-assessments. The TNA tools were developed using different methods such as expert panels, literature reviews, stakeholder interviews and quantitative surveys. Conclusion TNA is useful for defining and characterizing the public health workforce in every organization. Workforces consist of individuals who have their own training needs to fulfill their tasks. Therefore, individual and organizational TNA should be combined to study the public health workforce and their capacities. [ABSTRACT FROM AUTHOR]

Background The MONARCH 2 trial (NCT02107703) showed the efficacy of abemaciclib, a cyclin-dependent kinase 4 & 6 inhibitor (CDK4/6i), in combination with fulvestrant for hormone receptor-positive, HER2-negative metastatic breast cancer (MBC). The aim of this analysis was to explore the prediction of circulating tumor cells (CTCs) stratification using machine learning for hypothesis generation of biomarker-driven clinical trials. Patients and Methods Predicted CTCs were computed in the MONARCH 2 trial through a K nearest neighbor (KNN) classifier trained on a dataset comprising 2436 patients with MBC. Patients were categorized into predicted Stage IVaggressive (pStage IVaggressive, ≥5 predicted CTCs) or predicted Stage IVindolent (pStage IVindolent, <5 predicted CTCs). Prognosis was tested in terms of progression-free-survival (PFS) and overall survival (OS) through Cox regression. Results Patients classified as predicted pStage IVaggressive and predicted pStage Stage IVindolent were, respectively, 183 (28%) and 461 (72%). After multivariable Cox regression, predicted CTCs were confirmed as independently associated with prognosis in terms of OS, together with ECOG performance status, liver involvement, bone-only disease, and treatment arm. Patients in the pStage Stage IVindolent subgroup treated with abemaciclib experienced the best prognosis both in terms of PFS and OS. The treatment effect of abemaciclib on OS was then explored through subgroup analysis, showing a consistent benefit across all subgroups. Conclusion This study is the first analysis of CTCs modeling for stage IV disease stratification. These results show the need to expand biomarker profiling in combination with CTCs stratification for improved biomarker-driven drug development. [ABSTRACT FROM AUTHOR]